Laromustine, Daunorubicin, and Cytarabine in Treating Patients With Acute Myeloid Leukemia

May 12, 2011 updated by: Institut Paoli-Calmettes

A PHASE I-II MULTICENTER STUDY OF THE CLORETAZINE-DAUNORUBICIN-ARACYTINE COMBINATION FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA (AML) WITH UNFAVORABLE CYTOGENETICS

RATIONALE: Drugs used in chemotherapy, such as laromustine, daunorubicin, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of laromustine when given together with daunorubicin and cytarabine in treating patients with acute myeloid leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To determine the dose of laromustine that can be combined with daunorubicin hydrochloride and cytarabine in patients with previously untreated acute myeloid leukemia with unfavorable cytogenetics. (Phase I)
  • To determine the complete remission rate of this regimen as induction therapy. (Phase II)

Secondary

  • To determine the complete response rate.
  • To determine the safety profile of this regimen.
  • To determine the overall and relapse-free survival.
  • To evaluate the prognostic value of the molecular markers FLT3, duplications of MLL, and Evi-1.

OUTLINE: This is a multicenter, phase I dose-escalation study of laromustine followed by a phase II study.

  • Induction treatment: Patients receive laromustine IV on day 4, daunorubicin hydrochloride IV on days 1-3, and cytarabine IV continuously on days 1-7. Patients not attaining complete remission (CR) after first induction receive a second induction treatment comprising daunorubicin hydrochloride IV on days 1-3 and cytarabine IV twice daily on days 1-4. Patients in CR after 1 or 2 induction treatments proceed to consolidation treatment.
  • Consolidation treatment: Patients receive mini-consolidation treatment comprising amsacrine on day 1 and cytarabine IV twice daily on days 1-5 followed by 2 courses of continuing consolidation treatment comprising mitoxantrone hydrochloride on days 1 and 2 and cytarabine IV over 12 hours on days 1-5.
  • Allogeneic or autologous stem cell transplantation: Patients receive busulfan four times daily for 4 days and melphalan followed by allogeneic or autologous stem cell transplantation.

After completion of study treatment, patients are followed periodically for 5 years.

Study Type

Interventional

Enrollment (Anticipated)

135

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Marseille, France, 13273
        • Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of acute myeloid leukemia (AML)

    • Untreated disease
    • No promyelocytic AML

  • Unfavorable prognosis, defined as at least one of the following:

    • Cytogenetic abnormalities including -5/5q-, -7/7q-, 3q, 11q23, t(6;9), and complex abnormalities (≥ 3 clonal abnormalities), excluding t(9;11)
    • Baseline hyperleukocytosis ≥ 100 g/L or progression of leukocytosis or extra-medullary localizations despite treatment with hydroxyurea
  • No AML with favorable or intermediate prognosis
  • No AML secondary to myelodysplastic syndrome diagnosed within the past 3 months or myeloproliferative syndrome

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Total bilirubin < 35 μmol/L
  • Transaminases < 2.5 times upper limit of normal in the absence of leukemia-related abnormalities
  • Creatinine < 170 μmol/L OR creatinine clearance ≥ 50 mL/min in the absence of leukemia-related abnormalities
  • Not pregnant or nursing
  • Normal cardiac function by LVEF (echographic ≥ 40% or isotopic ≥ 50%)
  • Affiliated with a social security system

  • No uncontrolled or severe cardiovascular disease, including any of the following:

    • Myocardial infarction within the past 3 months
    • Cardiac insufficiency
    • Uncontrolled arrhythmia
  • No other active cancer within the past year except for basal cell carcinoma of the skin or epithelioma in situ of the cervix
  • No patients deprived of freedom or under guardianship (including temporary guardianship)
  • No psychological, familial, geographical, or social situations that preclude follow-up
  • No other contraindications to study treatment

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Prior hydroxyurea allowed
  • No concurrent disulfiram
  • No concurrent participation in another study with an experimental drug

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Dose-limiting toxicity (phase I)
Rate of complete remission (phase II)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Paoli-Calmettes

Investigators

  • Principal Investigator: Norbert Vey, MD, Institut Paoli-Calmettes

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Actual)

May 1, 2011

Study Registration Dates

First Submitted

February 7, 2009

First Submitted That Met QC Criteria

February 7, 2009

First Posted (Estimate)

February 10, 2009

Study Record Updates

Last Update Posted (Estimate)

May 13, 2011

Last Update Submitted That Met QC Criteria

May 12, 2011

Last Verified

July 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000634230
  • IPC-LAM-HR
  • IPC-2006-007
  • INCA-RECF0902
  • EUDRACT-2007-001082-15

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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